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J Virol, July 1998, p. 6104-6112, Vol. 72, No. 7
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Human Herpesvirus 6 Open Reading Frame U12 Encodes a Functional beta -Chemokine Receptor

Yuji Isegawa,1,* Zou Ping,1 Kazushi Nakano,1 Nakaba Sugimoto,2 and Koichi Yamanishi1

Department of Microbiology, Osaka University Medical School,1 and Department of Toxicology, Research Institute for Microbial Diseases, Osaka University,2 Suita, Osaka 565, Japan

Received 24 November 1997/Accepted 24 March 1998

Human herpesvirus 6 (HHV- 6), which belongs to the betaherpesvirus subfamily and infects mainly T cells in vitro, causes acute and latent infections. HHV- 6 contains two genes (U12 and U51) that encode putative homologs of cellular G-protein-coupled receptors (GCR), while three other betaherpesviruses, human cytomegalovirus, murine cytomegalovirus, and human herpesvirus 7, have three, one, and two GCR-homologous genes, respectively. The U12 gene is expressed late in infection from a spliced mRNA. The U12 gene was cloned, and the protein was expressed in cells and analyzed for its biological characteristics. U12 functionally encoded a calcium-mobilizing receptor for beta -chemokines such as regulated upon activation, normal T expressed and secreted (RANTES), macrophage inflammatory proteins 1alpha and 1beta (MIP-1alpha and MIP-1beta ) and monocyte chemoattractant protein 1 but not for the alpha -chemokine interleukin-8, suggesting that the chemokine selectivity of the U12 product was distinct from that of the known mammalian chemokine receptors. These findings suggested that the product of U12 may play an important role in the pathogenesis of HHV- 6 through transmembrane signaling by binding with beta -chemokines.

* Corresponding author. Mailing address: Department of Microbiology, Osaka University Medical School, 2-2 Yamada-oka, Suita, Osaka 565, Japan. Phone: 81-6-879-3323. Fax: 81-6-879-3329. E-mail: isegawa{at}micro.med.osaka-u.ac.jp.

J Virol, July 1998, p. 6104-6112, Vol. 72, No. 7
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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